According to the MR method in general, the body of the patient to be examined is arranged in a strong, uniform magnetic field B0 whose direction at the same time defines an axis (normally the z-axis) of the co-ordinate system on which the measurement is based. The magnetic field produces different energy levels for the individual nuclear spins in dependence on the magnetic field strength which can be excited (spin resonance) by application of an electromagnetic alternating field (RF field) of defined frequency (so-called Larmor frequency, or MR frequency). From a macroscopic point of view, the distribution of the individual nuclear spins produces an overall magnetization which can be deflected out of the state of equilibrium by application of an electromagnetic pulse of appropriate frequency (RF pulse) while the magnetic field of the RF pulse extends perpendicular to the z-axis, so that the magnetization performs a precession about the z-axis. This motion of the magnetization describes a surface of a cone whose angle of aperture is referred to as flip angle. The magnitude of the flip angle is dependent on the strength and the duration of the applied electromagnetic pulse. In the case of a so-called 90° pulse, the spins are deflected from the z axis to the transverse plane (flip angle 90°). The RF pulse is radiated toward the body of the patient via a RF coil arrangement of the MR device. The RF coil arrangement typically surrounds the examination volume in which the body of the patient is placed.
After termination of the RF pulse, the magnetization relaxes back to the original state of equilibrium, in which the magnetization in the z direction is built up again with a first time constant T1 (spin lattice or longitudinal relaxation time), and the magnetization in the direction perpendicular to the z direction relaxes with a second time constant T2 (spin-spin or transverse relaxation time). The variation of the magnetization can be detected by means of receiving RF coils which are arranged and oriented within the examination volume of the MR device in such a manner that the variation of the magnetization is measured in the direction perpendicular to the z-axis. The decay of the transverse magnetization is accompanied, after application of, for example, a 90° pulse, by a transition of the nuclear spins (induced by local magnetic field inhomogeneities) from an ordered state with the same phase to a state in which all phase angles are uniformly distributed (dephasing). The dephasing can be compensated by means of a refocusing pulse (for example a 180° pulse). This produces an echo signal (spin echo) in the receiving coils. Alternatively, the dephasing can be compensated by means of a magnetic gradient pulse, producing an echo signal (gradient echo) in the receiving coils. In order to realize spatial resolution in the body, linear magnetic field gradients extending along the three main axes are superposed on the uniform magnetic field, leading to a linear spatial dependency of the spin resonance frequency. The signal picked up in the receiving coils then contains components of different frequencies which can be associated with different locations in the body. The signal data obtained via the receiving coils corresponds to the spatial frequency domain and are called k-space data. The k-space data usually include multiple lines acquired with different phase encoding. Each line is digitized by collecting a number of samples. A set of k-space data is converted to a MR image by means of Fourier transformation.
In some medical applications, the difference in MR signal intensity from standard MR protocols, i.e. the contrast between different tissues, might not be sufficient to obtain satisfactory clinical information. In this case, contrast enhancing techniques are applied. A particularly promising approach for contrast enhancement and increase of MR detection sensitivity (by orders of magnitude) is the known method based on ‘Chemical Exchange Saturation Transfer’ (CEST), as initially described by Balaban et al. (see e.g. U.S. Pat. No. 6,962,769 B1) for the application to exogenously administered contrast agents. According to the CEST technique, the image contrast is obtained by altering the intensity of the water proton signal in the presence of a contrast agent or an endogenous molecule with a proton pool resonating at a different frequency than the main water resonance. This is achieved by selectively saturating the nuclear magnetization of the pool of exchangeable protons which resonate at a frequency different from the water proton resonance. Exchangeable protons can be provided by exogenous CEST contrast agents (e.g. DIACEST, PARACEST or LIPOCEST agents), but can also be found in biological tissue (i.e., endogenous amide protons in proteins and peptides, protons in glucose or protons in metabolites like choline or creatinine) A frequency-selective saturation RF pulse that is matched to the MR frequency (chemical shift) of the exchangeable protons is used for this purpose. The saturation of the MR signal of the exchangeable protons is subsequently transferred to the MR signal of nearby water protons within the body of the examined patient by chemical exchange with the water protons, thereby decreasing the water proton MR signal. The selective saturation at the MR frequency of the exchangeable protons thus gives rise to a negative contrast in a water proton based MR image. Amide proton transfer (APT) MR imaging, which is a CEST technique based on endogenous exchangeable protons, allows highly sensitive and specific detection of pathological processes on a molecular level, like increased protein concentrations in malignant tumor tissue. The APT signal is also sensitively reporting on locally altered pH levels—because the exchange rate is pH dependent—which can e.g. be used to characterize acidosis in ischemic stroke. APT/CEST MR imaging has several advantages over conventional MR contrasts. APT/CEST MR imaging allows highly specific detection and differentiation of endogenous contrasts, which is much more sensitive then e.g. spectroscopic MR/NMR techniques. This high sensitivity (SNR efficiency) can be used to obtain molecular contrast information at a resolution comparable to typical MR imaging applications in clinically acceptable examination times. Furthermore, CEST contrasts allow for multiplexing by using a single molecules or a mixture of molecules bearing exchangeable protons that can be addressed separately in a multi-frequency CEST MR examination. This is of particular interest for molecular imaging, where multiple biomarkers may be associated with several unique CEST frequencies. Moreover, the MR contrast in APT/CEST MR imaging can be turned on and off at will by means of the frequency selective preparation RF pulse. Adjustable contrast enhancement is highly advantageous in many applications, for example when the selective uptake of the contrast agent in diseased tissue in the examined body is slow, or for increasing the specificity of detection in areas with highly structured basic MR contrast.
In conventional APT and CEST MR imaging, the effect of the saturation transfer of exchangeable protons to water is identified by an asymmetry analysis of the amplitude of the acquired MR signals as a function of the saturation frequency. This asymmetry analysis is performed with respect to the MR frequency of water protons, which, for convenience, is assigned to a saturation frequency offset of 0 ppm. The measurement of the amplitude of the acquired MR signals as a function of the saturation frequency offset and the asymmetry analysis are inherently very sensitive to any inhomogeneity of the main magnetic field B0. This is because a small shift of the center frequency (e.g. a saturation frequency offset of 0.1 ppm relative to the chemical shift of water) easily causes a variation of more than 10% in the asymmetry data. This variation results in large artifacts in the finally reconstructed APT/CEST MR images.
It has been shown (e.g. Zhou et al., Magnetic Resonance in Medicine, 60, 842-849, 2008) that the B0 inhomogeneity can be corrected in APT/CEST imaging on a voxel-by-voxel basis through re-centering of the asymmetry data on the basis of a separately acquired B0 map. However, an additional B0 mapping scan is required in this known approach. This results in an extended overall imaging time. Several other known methods to correct for B0 inhomogeneity require additional overall scan time to obtain the necessary B0 field inhomogeneity information (e.g. WASSR). Moreover, the separately performed measurement of to obtain the B0 inhomogeneity information is potentially inaccurate or inconsistent, for example because of patient motion, shimming or frequency drift of the used MR device between the field mapping and the actual APT/CEST acquisition. Consequently, the B0 map has to be acquired in close temporal proximity to the APT/CEST scan and potentially needs to be repeated, for example in order to ensure sufficient precision in case of multiple APT/CEST scans within one examination. Thus, the known technique may be severely limited for clinical applications with respect to scan time efficiency and precision.
Another issue in APT and CEST MR imaging is that a robust elimination of signal contributions from fat spins, e.g. by fat saturation RF pulses, is often difficult in the presence of B0 inhomogeneity. However, residual fat signal contributions result in a strongly biased asymmetry of the amplitude of the acquired MR signals as a function of the saturation frequency offset near the chemical shift of fat protons at −3.4 ppm relative to the MR frequency of water protons. This is of particular concern in applications in which MR images of organs with significant fat content are to be acquired, such as the liver or the breast.
The ISMRM 2010 abstract ‘CEST-Dixon MRI for sensitive and accurate measurement of amide proton transfer in human 3T’ by J. Keupp and H. Eggers discloses a multi-echo T1-weighted gradient echo sequence to acquire APT/CEST MRI. This known approach also employs an iterative Dixon technique to map local field inhomogeneities based on a multi-echo gradient echo approach. This approach provides a B0 field map acquired during the actual APT/CEST acquisition and thus solves some of the above mentioned issues related to additional scan time and workflow/timing for the field mapping as well as the precision of the field characterization,